Until recent years it was believed that the functions of the digestive system were controlled by the two classical divisions of the autonomic nervous system acting in concert with established gastrointestinal hormones. However, advances in immunohistochemistry has suggested that peptide-producing neurons may also exert local regulation of the gut function. In the past decade, a rapidly expanding array of putative neuropeptides have been identified and an even larger number of biological effects have been reported. Unfortunately, it has been difficult to demonstrate the ways in which these newer peptide systems might interact with the established divisions of the autonomic nervous system and to establish the physiological relevance of the observed effects. In many cases, these newly discovered neuropeptides remain agents in search of physiological functions. Current investigations suggest that peptide- containing neurons have crucial roles in human physiology and may be involved in abnormalities of gastrointestinal function. The current research proposal is designed to investigate, on a fundamental level, the actions of two important neuropeptides, calcitonin gene-related peptide and neuropeptide Y. These two peptides were specifically chosen because they demonstrate reciprocal, often opposing, actions within the enteric nervous system. Calcitonin gene-related peptide and neuropeptide Y thus compose an attractive model for the study of enteropancreatic nervous function. The proposed research is designed to integrate physiological studies with important advances in cellular and molecular biology. This approach is believed to be likely to yield significant new insights into human health and disease. It is hoped that studies of these two opposing peptides may serve as a model for similar investigations of other neuropeptides that affect digestive function.